IMPAACT P1063: Safety and Effectiveness of Atorvastatin in HIV Infected Children and Adolescents With Hyperlipidemia

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ClinicalTrials.gov Identifier: NCT00663234

Recruitment Status
:
Terminated
(The study was prematurely discontinued due to administrative reasons.)

Treatment of HIV with combination antiretroviral regimens frequently results in the suppression of HIV viral load, significant immune recovery, and delayed disease progression. However, treatment with these regimens, particularly protease inhibitors (PIs), has been associated with significant increases in cholesterol and triglycerides in HIV-infected adults and children. The purpose of this study was to evaluate the safety and effectiveness of escalating doses of atorvastatin, a FDA-approved drug which lowers cholesterol and triglyceride levels, in HIV-infected children receiving stable antiretroviral regimens.

Condition or disease

Intervention/treatment

Phase

HIV InfectionsHyperlipidemia

Drug: Atorvastatin

Phase 1Phase 2

Detailed Description:

Antiretroviral regimens, particularly those containing PIs, often cause hyperlipidemia, which is an increase in the amount of fat (such as cholesterol and triglycerides) in the blood. These increases can lead to heart disease and pancreatitis. Although the mechanism by which PIs cause hyperlipidemia is not clearly understood, there are medications to combat this side effect. The primary purpose of this study was to evaluate the safety and effectiveness of escalating doses of atorvastatin, based on low-density lipoprotein cholesterol (LDL-C) levels, in HIV-infected children receiving stable antiretroviral therapy.

Participants were assigned to one of two groups based on age (10 to 14 years or 15 to 23 years) and were treated for a maximum of 48 weeks. The first six participants enrolled in the study were in the 15 to 23 year old age group. Once safety data through week 8 on these 6 participants was analyzed, the remaining participants were enrolled. All participants received atorvastatin in combination with a stable antiretroviral regimen. Each participant was followed independently according to a dose escalation algorithm for atorvastatin. Participants began dosing at 10 mg daily. If efficacy criteria were not met, dosing increased to 20 mg daily at week 8. Since dose escalations were done within subject, safety and efficacy rates were presented for the dose-escalation strategy overall and not for individual doses. Atorvastatin was provided by the study, but antiretrovirals were not.

AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see references in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening, Grade 5=Death. Relationship to study treatment was determined by the core study team. The primary outcome measure includes any AE of grade 3 or higher and liver function tests (LFTs) of grade 2 or higher.

Percentage of Participants Experiencing at Least One Treatment-related Adverse Event (AE) by Age Group [ Time Frame: Study entry to weeks 12, 24, and 48 ]

AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see references in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening, Grade 5=Death. Relationship to study treatment was determined by the core study team. The primary outcome measure includes any AE of grade 3 or higher and liver function tests (LFTs) of grade 2 or higher.

Percentage of Participants Experiencing at Least One Adverse Event (AE) by Age Group [ Time Frame: Study entry to weeks 12, 24, and 48 ]

AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see references in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening, Grade 5=Death. The primary outcome measure includes any AE of grade 3 or higher and liver function tests (LFTs) of grade 2 or higher.

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Ages Eligible for Study:

10 Years to 23 Years (Child, Adult)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

A diagnosis of HIV-1 infection

CD4 % of at least 15 at screening

HIV-1 viral load of less than 10,000 copies/ml at screening

On a stable antiretroviral therapy regimen for at least 6 months

Tanner stage of 2 or higher

At least two LDL-C measurements of 130 mg/dL or higher over the 6 months prior to screening and after documented attempts at modifying diet and other risk factors. More information on this criterion can be found in the protocol.

Able to fast overnight for 8 hours

Negative pregnancy test at screening

Agree to use two appropriate forms of contraception (female participants). More information on this criterion can be found in the protocol.

Exclusion Criteria:

Certain abnormal laboratory values

Any laboratory or unresolved clinical toxicity of Grade 3 or higher

Unlikely to remain on current antiretroviral therapy for at least six months after study entry

Use of statin, fibrate, or niacin within 3 months prior to study entry

Evidence of chronic ongoing myositis or history of myopathy or neuromuscular disorder